DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
Acknowledgement is made of application 16/846,297 filed April 11th, 2020. The effective filing date is April 11th, 2020.
Status of Claims
Claims 1-20 are currently pending and examined on the merits.
Information Disclosure Statement
The Information Disclosure Statement(s) is/are acknowledged and the references contained therein have been considered by the Examiner. This includes the Information Disclosure Statements(s) filed on: June 8th, 2023.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea of mental steps, mathematic concepts, organizing human activity, or a natural law without significantly more.
Step 2A, Prong 1
In accordance with MPEP § 2106, claims found to recite statutory subject matter (claim 1-20 are drawn to a system) (Step 1: YES) are then analyzed to determine if the claims recite any concepts that equate to an abstract idea, law of nature or natural phenomenon (Step 2A, Prong 1). In the instant application, the claims (listed numerically) recite the following limitations that equate to an abstract idea (reasonings in parentheses):
Claim 1 states:
analyze data obtained by single cell sequencing of cells along with molecular probes…, (which is a mental step, i.e. can be completed with pen and paper)
Claim 6 and 16 states: the processor device is further implemented to: identify individual ones of the cells by the cell barcode…(mental step)
Claim 7 and 17 states: wherein the processor device is further implemented to: identify an original position of the cells within the biological sample via the oligonucleotide sequence…(mental step)
Claim 8 states: the processor device is further implemented to:collect transcriptome information of the cells…(mental step)
Claim 11 states:
analyze data obtained by single cell sequencing of cells along with molecular probes (mental step)
collect from the data concomitant spatial and molecular measurements of one or more of the cells in the biological sample (mental step)
The claims recite an abstract idea of analyzing genomic sequencing data (See MPEP 2106.07(a)).
These recitations are similar to the concepts of collecting information, analyzing it and displaying certain results of the collection and analysis in Electric Power Group, LLC, v. Alstom (830 F.3d 1350, 119 USPQ2d 1739 (Fed. Cir. 2016)), organizing and manipulating information through mathematical correlations in Digitech Image Techs., LLC v Electronics for Imaging, Inc. (758 F.3d 1344, 111 U.S.P.Q.2d 1717 (Fed. Cir. 2014)) and comparing information regarding a sample or test to a control or target data in Univ. of Utah Research Found. v. Ambry Genetics Corp. (774 F.3d 755, 113 U.S.P.Q.2d 1241 (Fed. Cir. 2014)) and Association for Molecular Pathology v. USPTO (689 F.3d 1303, 103 U.S.P.Q.2d 1681 (Fed. Cir. 2012)) that the courts have identified as concepts that can be practically performed in the human mind or mathematical relationships. Therefore, these limitations fall under the “Mental process” and “Mathematical concepts” groupings of abstract ideas.
There are no additional limitations that indicate that the claims require anything other than carrying out the recited mental process or mathematical concept in a generic computer environment. Merely reciting that a mental process is being performed in a generic computer environment does not preclude the steps from being performed practically in the human mind or with pen and paper as claimed. If a claim limitation, under its broadest reasonable interpretation, covers performance of the limitation in the mind but for the recitation of generic computer components, then if falls within the “Mental processes” grouping of abstract ideas. As such, claim(s) 1-16 recite(s) an abstract idea/law of nature/natural phenomenon (Step 2A, Prong 1: YES).
Step 2A, Prong 2
Claims found to recite a judicial exception under Step 2A, Prong 1 are then further analyzed to determine if the claims as a whole integrate the recited judicial exception into a practical application or not (Step 2A, Prong 2). This judicial exception is not integrated into a practical application because the claims do not recite an additional element that reflects an improvement to technology or applies or uses the recited judicial exception to affect a particular treatment for a condition. Rather, the instant claims recite additional elements that amount to mere instructions to implement the abstract idea in a generic computing environment or mere instructions to apply the recited judicial exception via a generic treatment. Specifically, the claims recite the following additional elements:
Claim 2 and 12 states: the cells have been disassociated from the biological sample for the single cell sequencing.…
Claim 3 and 13 states: the molecular probes retain the positional data of the cells that have been disassociated from the biological sample… the molecular probes retain the positional data of the cells that have been disassociated from the biological sample.
Claim 4 and 14 states: the molecular probes comprise an oligonucleotide sequence that uniquely encodes the position of the cells in the biological sample…
Claim 5 and 15 states: wherein the molecular probes further comprise:a polymerase chain reaction (PCR) handle; a cell barcode; and a unique molecular identifier (UMI)…
Claim 9 and 19 states: the biological sample is selected from the group consisting of: a cell culture, a tissue sample, and combinations thereof.
Claim 10 and 20 states: the single cell sequencing of the cells is performed using a technique selected from the group consisting of: drop-seq, seq-well, cyto-seq, and combinations thereof.
Claim 18 states: the molecular measurements comprise transcriptome information of the cells.
There are no limitations that indicate that the claimed analysis engine or the formats of the provided data require anything other than generic computing systems. As such, these limitations equate to mere instructions to implement the abstract idea on a generic computer that the courts have stated does not render an abstract idea eligible in Alice Corp., 573 U.S. at 223, 110 USPQ2d at 1983. As such, claims 1-20 are directed to an abstract idea (Step 2A, Prong 2: NO).
Step 2B
Claims found to be directed to a judicial exception are then further evaluated to determine if the claims recite an inventive concept that provides significantly more than the judicial exception itself (Step 2B). The claims do not include additional elements that are sufficient to amount to significantly
more than the judicial exception because the claims recite additional elements that equate to mere
instructions to apply the recited exception in a generic way or in a generic computing environment. The
instant claims recite the following additional elements:
Claim 3 and 13 states: the molecular probes retain the positional data of the cells that have been disassociated from the biological sample… the molecular probes retain the positional data of the cells that have been disassociated from the biological sample.
Claim 4 and 14 states: the molecular probes comprise an oligonucleotide sequence that uniquely encodes the position of the cells in the biological sample…
Claim 5 and 15 states: wherein the molecular probes further comprise: a polymerase chain reaction (PCR) handle; a cell barcode; and a unique molecular identifier (UMI)…
Claim 10 and 20 states: the single cell sequencing of the cells is performed using a technique selected from the group consisting of: drop-seq, seq-well, cyto-seq, and combinations thereof.
Regarding claims 3-5, 10, 13-15 and 20, the steps of analyzing single cell sequencing data does not integrate the abstract idea into a practical application and constitutes an insignificant extra-solution activity (i.e., data gathering and presentation), which does not impose a meaningful limit on the abstract idea (see MPEP 2106.05 (g)).
As discussed above, there are no additional limitations to indicate that the claimed
analysis requires anything other than generic computer components in order to carry out the recited abstract idea in the claims. Claims that amount to nothing more than an instruction to apply the abstract idea using a generic computer do not render an abstract idea eligible. Alice Corp., 573 U.S. at 223, 110 USPQ2d at 1983. See also 573 U.S. at 224, 110 USPQ2d at 1984. MPEP 2106.05(f) discloses that mere instructions to apply the judicial exception cannot provide an inventive concept to the claims.
Additionally, the claims are directed to well-understood, routine, and conventional activity as evidenced by:
Kulkarni et al. (Curr Opin Biotechnol. 2019 August ; 58: 129–136.), which reviews single cell transcriptomics and UMI,
Sibo Zhu et al. (Oncotarget, 2017, Vol. 8, (No. 32), pp: 53763-53779), which reviews Advances in single-cell RNA sequencing and its applications in cancer research, including drop-seq and cyto-seq, and,
Teves et al. (Mol. Cells 2020; 43(7): 591-599), which reviews advances in spatial transcriptomics technology to map the position of cells using probes.
The additional elements do not comprise an inventive concept when considered individually or
as an ordered combination that transforms the claimed judicial exception into a patent-eligible application of the judicial exception. Therefore, the claims do not amount to significantly more than the
judicial exception itself (Step 2B: No). As such, claims 1-20 is/are not patent eligible.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-20 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kenneth Hu et al. (BioRxiv. Feb 2020. Pg. 1-62).
Regarding claims 1 and 11, Hu et al. teaches ZipSeq a single cell sequencing method using patterned illumination and photocaged oligonucleotides to serially print barcodes (‘zipcodes’) onto live cells in intact tissues, in real time and with an on-the-fly selection of patterns, and using Illumina HiSeq and NovaSeq. Using ZipSeq, Hu et al. mapped gene expression in three settings: in vitro wound healing, live lymph node sections and a live tumor microenvironment (pg. 2-3, pg. 23-24, Abstract, introduction, re: clm. 1, … A system, comprising: a processor device, connected to a memory, that is implemented to: analyze data obtained by single cell sequencing of cells along with molecular probes, that have been delivered inside the cells, which uniquely encode a position of the cells in a biological sample…, clm. 11, …A system, comprising: a processor device, connected to a memory, that is implemented to: analyze data obtained by single cell sequencing of cells along with molecular probes, that have been delivered inside the cells, which uniquely encode a position of the cells in a biological sample; and collect from the data concomitant spatial and molecular measurements of one or more of the cells in the biological sample.). Hu teaches spatial transcriptomics with barcoding in anticipation of claim 1.
Regarding claims 2 and 12, Hu et al. details isolation of murine tumor segments and processing of said segments for FACS sorting in the methods of pg. 23 and in Fig. 1 (pg. 33-34), which is equivalent to disassociating cells from a sample (re: clm. 2, 12 … wherein the cells have been disassociated from the biological sample for the single cell sequencing.). Hu et al. anticipates claims 2 and 12.
Regarding claim 3, 13 Hu et al. details labeling of disassociated single cells in Fig. 1, and a differential expression analysis within populations based on position in Fig. 3 (pg. 39-40) (re: clm. 3, 13 … wherein the molecular probes encode positional data comprising the position of the cells in the biological sample, and wherein the molecular probes retain the positional data of the cells that have been disassociated from the biological sample.). Hu et al. details a spatial single cell transcriptomics analysis in anticipation of claims 3 and 13.
Regarding claims 4-6, and 14-16 Hu et al. details an analysis of unique molecular identifiers per cell in Fig. 2 (pg. 36-38, inclusive of barcoding and a PCR reaction), oligonucleotides used in the methods on pgs. 17-19 (Oligonucleotide list), and an imaging analysis per cell type on Fig. 5 (pg. 44-46) in which individual cells are identified per barcode (re: clm. 4, 14 … wherein the molecular probes comprise an oligonucleotide sequence that uniquely encodes the position of the cells in the biological sample…, clm. 5,15 … wherein the molecular probes further comprise: a polymerase chain reaction (PCR) handle; a cell barcode; and a unique molecular identifier (UMI)…, clm. 6,16 … the processor device is further implemented to: identify individual ones of the cells by the cell barcode.) Hu et al. anticipates claims 4-6 and 14-16
Regarding claims 7-10 and 17-20, Hu et al. details original positions of cells (derived from a tissue sample) using oligonucleotide sequences as detailed on pg. 3-4:
“…we sought to use existing scRNA-Seq workflows and to develop a method for ‘printing’ a DNA barcode onto live cells in a spatially defined manner, which can be read-out during sequencing…We accomplished this by initially coating a base DNA oligo onto cells in a tissue and –through photocaging—we could control hybridization of subsequent DNA strands in a light- and thus spatially-restricted manner. The resultant barcodes then provided a connection to those user defined regions.”
Hu et al. further teaches, a differential expression analysis in Fig. 2, highlighting relevant gene expression enrichment per position (pg. 36-37, re: clm. 7, 17 … wherein the processor device is further implemented to: identify an original position of the cells within the biological sample via the oligonucleotide sequence…, clm. 8,18 … wherein the processor device is further implemented to:collect transcriptome information of the cells…, clm. 9,19 … wherein the biological sample is selected from the group consisting of: a cell culture, a tissue sample, and combinations thereof.).
Hu et al. additionally discloses that ZipSeq can be utilized with droplet based scRNA-seq methods on pg. 14 (re: clm. 10, 20 , … wherein the single cell sequencing of the cells is performed using a technique selected from the group consisting of: drop-seq, seq-well, cyto-seq, and combinations thereof.). Hu et al. teaches a drop-seq enabled spatial transcriptomics method in anticipation of claims 7-10 and 17-20.
Conclusion
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/J.T.S./Examiner, Art Unit 1686
/Karlheinz R. Skowronek/Supervisory Patent Examiner, Art Unit 1687
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